Qidong hepatitis B virus infection cohort: a 25-year prospective study in high risk area of primary liver cancer.

Qidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P < 0.0001) in HBsAg-positive arm compared with HBsAg-negative arm. The relative risk of PLC was 13.25 (95% CI=6.67-26.33, P < 0.0001) and 28.05 (95% CI=13.87-56.73, P < 0.0001) in the HBsAg+/HBeAg- group and the HBsAg+/HBeAg+ group, respectively, as compared to the HBsAg-/HBeAg- group. A series of novel PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.

Formation of Mn-Co-Ni-O Nanoceramic Microspheres Using In Situ Ink-Jet Printing: Sintering Process Effect on the Microstructure and Electrical Properties.

Mn-Co-Ni-O nanoceramic microspheres with high density, uniformity, and size tunability are successfully fabricated using in situ ink-jet printing and two step sintering (TSS) techniques. The microspheres, synthesized by an effective and facile reverse microemulsion method, consist of uncalcined Mn-Co-Ni-O nanocrystallines that show a well formed single tetragonal spinel phase and an average particle size distribution of ≈20 nm. The sintering behavior, microstructure, and electrical properties of the Mn-Co-Ni-O nanoceramic microspheres are systematically investigated and characterized. The results indicate that the sintered Mn-Co-Ni-O nanoceramic microspheres show high density and improved electrical properties. The highest R25 , B25/50 , Ea , and α25 values achieved at sintering temperature of 1150 °C are 4846.7 KΩ, 4320 K, 0.401 eV, and -5.24% K-1 , respectively for these Mn-Co-Ni-O nanoceramic microspheres. Furthermore, the formation mechanism of uncalcined Mn-Co-Ni-O nanocrystallines and an analysis of the TSS procedure of the nanoceramic microspheres are discussed.

[Family history of liver cancer increases the risk of liver cancer incidence: a 20-year prospective cohort study in Qidong, China].

OBJECTIVE: To evaluate whether first-degree family history of liver cancer plays a role in liver cancer incidence by prospective evaluation of a patient cohort in Qidong, China over a 20-year period. METHODS: In May 1992, 708 hepatitis B surface antigen (HBsAg) carriers and 730 HBsAg-negadve controls from Qidong city were enrolled for participation in a prospective cohort study ending in November 2012.Follow-up was carried out every 6 to 12 months, and evaluations included serum assays to measure concentrations of alpha fetoprotein (AFP), HBsAg and alanine aminotransferase (ALT), as well as abdominal ultrasound to assess liver disease.The relationship between baseline (study entry) information of patients with first-degree family history of liver cancer and liver cancer incidence during the two decades of study was statistically assessed. RESULTS: There were 172 newly diagnosed liver cancer cases in the cohort during 25 753 person-years (py) of follow-up, representing an incidence of 667.88/100 000 py.The incidence rates of liver cancer among participants with or without liver cancer family history were 1 244.36/100 000 py and 509.70/100 000 py respectively, and the between-group difference reached the threshold for statistical significance (P less than 0.01, Relative Risk (RR):2.44, 95% Confidence Interval (CI):1.80-3.31).The incidence rates of liver cancer among participants who had a sibling with liver cancer and participants who had a parent with liver cancer were not significantly different (P > 0.05), but the liver cancer incidence among participants who had a mother with liver cancer was significantly higher than that of participants who had a father with liver cancer (P < 0.05, RR:1.86, 95% CI:1.03-3.36). Among the participants with liver cancer family history, 56.52% (39/69) were diagnosed before 50 years old, and this rate was significantly higher than that of participants without a family history of liver cancer (40.78%, 42/103, P less than 0.05).The incidence rate of liver cancer among the participants who were family history-positive and HBsAg-positive was significantly higher than that of participants who were family history-negative but HBsAg-positive (P < 0.01, RR:1.75, 95% CI:1.29-2.38), and was 59.59 times higher than for participants who were family history-negative and HBsAgnegative.Subgroup analysis of liver cancer incidence among participants who were family history-positive but HBsAg-negative and participants who were family history-negative and HBsAg-negative produced anRR of 2.60, but there was no statistically significant difference between the two subgroups (P > 0.05).At the study's end, the incidence rates of liver cancer for the different subgroups were 32.21% for the family history-positive and HBsAgpositive participants, 19.80% for the family history-negative and HBsAg-positive participants, 1.71% for the family history-positive and HBsAg-negative participants, and 0.65% for the family history-negative and HBsAg-negative participants. CONCLUSION: First-degree family history of liver cancer is a risk factor of liver cancer in Chinese patients from Qidong, and exhibits synergism with HBsAg-positivity for incidence of liver cancer.

Dramatic reduction of liver cancer incidence in young adults: 28 year follow-up of etiological interventions in an endemic area of China.

Qidong City, China, has had high liver cancer incidence from endemic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin. Based on etiologic studies, we began interventions in 1980 to reduce dietary aflatoxin and initiate neonatal HBV vaccination. We studied trends in liver cancer incidence rates in the 1.1 million inhabitants of Qidong and examined trends in aflatoxin exposure, staple food consumption, HBV infection markers and annual income. Aflatoxin exposure declined greatly in association with economic reform, increased earnings and educational programs to shift staple food consumption in the total population from moldy corn to fresh rice. A controlled neonatal HBV vaccination trial began in 1983 and ended in November, 1990, when vaccination was expanded to all newborns. Liver cancer incidence fell dramatically in young adults. Compared with 1980-83, the age-specific liver cancer incidence rates in 2005-08 significantly decreased 14-fold at ages 20-24, 9-fold at ages 25-29, 4-fold at ages 30-34, 1.5-fold at ages 35-39, 1.2-fold at ages 40-44 and 1.4-fold at ages 45-49, but increased at older ages. The 14-fold reduction at ages 20-24 might reflect the combined effects of reduced aflatoxin exposure and partial neonatal HBV vaccination. Decrease incidence in age groups >25 years could mainly be attributable to rapid aflatoxin reduction. Compared with 1980-83, liver cancer incidence in 1990-93 significantly decreased 3.4-fold at ages 20-24, and 1.9-fold at ages 25-29 when the first vaccinees were <11 years old.

[Relationship between serum hepatitis B virus DNA load and hepatocellular carcinoma in Qidong, China: a cohort follow-up study of 14 years].

OBJECTIVE: To explore the relationship between serum HBV DNA load and hepatocellular carcinogenesis in Qidong HBsAg carriers. METHODS: In 1997, 477 HBsAg carriers and 477 age, gender and residence matched HBsAg negative controls were enrolled as a prospective cohort in Qidong city. The entry serum samples were detected for the levels of HBeAg and HBV DNA. The relationship between baseline HBV DNA load and hepatocellular carcinoma (HCC) during the follow-up period from June 1997 to June 2011 were analyzed. RESULTS: The total observed person-years (PY) were 12 200. Eighty-seven patients developed HCC with an incidence of 1498/100 000 PY in the HBsAg positive group versus 6 with an incidence of 94/100 000 PY (P = 0.000) in the HBsAg negative group. The relative risk (RR) was 15.96. N o significant difference existed between the incidences of other tumors in two groups (P = 0.161). Compared with the HBsAg negative group, the RR of HCC was 11.38 (95%CI 4.87 - 26.62, P < 0.01)in the HBsAg+/HBeAg- group and 29.08 (95%CI 12.37 - 68.37, P < 0.01) in the HBsAg+/HBeAg+ group; 5.80 (95%CI 2.29 - 14.70, P < 0.01) in the HBsAg+/HBV DNA- group and 27.75 (95%CI 12.07 - 63.81, P < 0.01) in the HBsAg+/HBV DNA+ group. In HBsAg positive subjects, while the HBV DNA load was classified into 5 levels namely 250 - 10(4), 10(4)-, 10(5)-, 10(6)- and ≥ 10(7) copies/ml, the relative risks for HCC at each level were 2.84 (95%CI 1.44 - 5.61, P < 0.01), 5.75 (95%CI 2.77 - 11.95, P < 0.01), 9.05 (95%CI 4.71 - 17.41, P < 0.01), 6.39 (95%CI 2.79 - 14.64, P < 0.01) and 4.35 (95%CI 2.21 - 8.56, P < 0.01) respectively versus the < 250 copies/ml group. CONCLUSION: HBV DNA is an important risk predictor of hepatocellular carcinoma. The HBsAg carriers with the serum loads of HBV DNA between 10(5) - 10(6) copies/ml are most likely to present with HCC.

Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.

The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD), however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum) using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO). In addition, the relationship between the changes of axons and the expression of ß-amyloid 42 (Aß42) and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aß plaques or overexpression of Aß42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.

[Longitudinal study of aflatoxin exposure in the development of primary liver cancer in patients with chronic hepatitis].

OBJECTIVE: To study the relationship between aflatoxin exposure and the development of primary liver cancer (PLC) in patients with chronic hepatitis. METHODS: A 21-year longitudinal study was carried out in a large cohort of 515 PLC high-risk individuals with HBV infection in PLC high prevalence region. RESULTS: (1) The PLC year-incidence of cohort was 1437.25/100,000. And it was significantly higher than that of the same natural peoples (184. 53/100,000, P = 0.000, RR = 7.79). There was no significant difference in the incidence of other tumors between these two groups (P = 0.576). (2) The PLC patients in the cohort were diagnosed at an average age 1.4 year younger than those in the same natural peoples and had an average survival of 6.42 months longer than the latter. (3) The PLC year-incidence of those with the exposure to aflatoxin was significantly higher than that of unexposed people (2784. 96/100,000 vs. 1251.02/100,000, P = 0.008, RR = 2.23). There was no relationship between the incidence rate of other tumors and the aflatoxin exposure. (4) The PLC year-incidence of aflatoxin-exposing people increased with the rising urine excretion of AFM1. When the urine excretion of AFM1 was more than 100 ng during 24 hours, the PLC year-incidence was high as 4717.82/100,000. The urine excretion of AFM1 was also obviously related with the abnormal liver function (P = 0.035). There was no relationship with the positive rate of HBeAg (P = 0.812). (5) The PLC year-incidence of those with the exposure to aflatoxin were infected with HBV (2 784. 96/100 000) significantly higher than that of cohort people (P = 0.001) and the same natural peoples (P = 0.000, RR = 15.09). (6) It took an average time of 14.65 years (median 13.68) from hepatitis occurrence to PLC diagnosis and 7.38 years (median 6.40) from liver cirrhosis to PLC diagnosis. CONCLUSION: HBV infection is a main etiological factor of PLC and the aflatoxin exposure has obvious synergistic effect in the carcinogenesis of PLC. Regular observation in a PLC high-risk cohort is effective for an early diagnosis and treatment. Hepatitis control and aflatoxin de-pollution is effective to inhibit the occurrence of PLC.

Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China.

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing either 400 or < 3 micromol glucoraphanin nightly for 2 weeks. Adherence to the study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin-N(7)-guanine were not different between the two intervention arms (P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and showed a robust inverse association with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed (P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions.